Functional plasticity of glutamatergic neurons of medullary reticular nuclei after spinal cord injury in mice

Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation after a lateral thoracic hemisection in female mice. Sites evoking stronger excitatory descending drive in intact conditions are the most impaired after injury, whereas those associated with a weaker drive are potentiated. After lesion, pro- and anti-locomotor activities (that is, initiation/acceleration versus stop/deceleration) are overall preserved. Activating the descending reticulospinal drive improves stepping ability on a flat surface of chronically impaired injured mice, and its priming enhances recovery of skilled locomotion on a horizontal ladder. This study highlights the resilience and capacity for reorganization of the glutamatergic reticulospinal command after injury, along with its suitability as a therapeutical target to promote functional recovery.


Statistics
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Reporting for specific materials, systems and methods
We require information from authors about some types of materials, experimental systems and methods used in many studies.Here, indicate whether each material, system or method listed is relevant to your study.If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.No sample size computation was performed.Changes were statistically assessed on a longitudinal basis for each animal to evaluate the diversity of changes (no changes, depression, potentiation).With a sample of about 7-11 individuals for each of the four lateral positions, between-groups differences could have been detected using ANOVA or Kruskal-Wallis.Also, this sample size per group is usually reported in other locomotor studies, including our owns (Lemieux and Bretzner, 2019;Josset et al., 2018;Roussel et al., 2023).

Materials & experimental systems
Two mouse were excluded after anatomical analysis.Position of implants were deemed too dorsal to be relevant.
Due to the longitudinal aspect of the study, each mouse is an experiment.Each mouse was sampled at least 4 times: (session) before injury for baseline and after 1, 3 and 7 weeks over a period of 3 months.For each mouse and session, measures were replicated 10-25 times for EMG response at rest ( Mice were randomly allocated to experimental groups (mediolateral position).
Blinding was not possible because experimenters performed both surgeries and data collection.Furthermore, it was possible to judge the group with the lateral position of the implant.All mice underwent the same protocole and data was analyzed the same way.